Epidemiologic studies have identified a positive association between obesity and colorectal neoplasia. Adiposity induces systemic low-grade inflammation, which is commonly assessed with a sensitive biomarker, C-reactive protein (CRP). To understand the molecular mechanisms of obesity in the etiology of colorectal neoplasia, the present study was conducted in 782 adenoma cases and 738 controls who underwent total colonoscopy, and their plasma CRP level was evaluated in relation to colorectal adenoma prevalence. A logistic regression model was used to compute odds ratios (OR) and 95% confidence intervals (CI) of adenoma according to quartile of plasma CRP. Plasma CRP level was positively associated with higher adenoma prevalence in all subjects (OR 1.30; 95% CI 0.94-1.79 for the highest versus lowest quartile; P trend = 0.031). Further analysis by adenoma size and number revealed a pronounced association with a larger size (≥5 mm) and multiple numbers (≥2). These positive associations were reduced to non-significance following further adjustment for body mass index, and OR for the highest versus lowest quartile of plasma CRP became 1.12 (95% CI 0.80-1.56; P trend = 0.25) in all subjects. In conclusion, this study suggests that obesity-related systemic low-grade inflammation may play an important role in the early stages of colorectal carcinogenesis.